dbSNP rs869312863: UHMK1:p.Pro405Arg (chr1-162522504-C-G) – ACMG Classification: Uncertain_significance (5 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM5PP3

The NM_175866.5(UHMK1):c.1214C>G(p.Pro405Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P405L) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

UHMK1
NM_175866.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.92

Variant links:

Genes affected

UHMK1 (HGNC:19683): (U2AF homology motif kinase 1) The gene encodes a serine/threonine protein kinase that promotes cell cycle progression through G1 by phosphorylation of the cyclin-dependent kinase inhibitor 1B (p27Kip1), which causes nuclear export and degradation. The encoded protein is also thought to function in the adult nervous system and the gene has been associated with schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

UHMK1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr1-162522504-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 224812.Status of the report is criteria_provided_single_submitter, 1 stars.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.808

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UHMK1	NM_175866.5 link	c.1214C>G	p.Pro405Arg	missense_variant	Exon 8 of 8	ENST00000489294.2	NP_787062.1	Q8TAS1-1
UHMK1	NM_001184763.1 link	c.992C>G	p.Pro331Arg	missense_variant	Exon 8 of 8		NP_001171692.1	Q8TAS1-3
UHMK1	NM_144624.2 link	c.*90C>G		3_prime_UTR_variant	Exon 7 of 7		NP_653225.2	Q8TAS1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UHMK1	ENST00000489294.2 link	c.1214C>G	p.Pro405Arg	missense_variant	Exon 8 of 8	1	NM_175866.5	ENSP00000420270.1	Q8TAS1-1
UHMK1	ENST00000538489.5 link	c.*90C>G		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000446416.1	Q8TAS1-2
UHMK1	ENST00000545294.5 link	c.992C>G	p.Pro331Arg	missense_variant	Exon 8 of 8	2		ENSP00000441226.1	Q8TAS1-3
UHMK1	ENST00000282169.8 link	n.1795C>G		non_coding_transcript_exon_variant	Exon 7 of 7	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

.;D

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.81

D;D

MetaSVM

Uncertain

0.33

MutationAssessor

Pathogenic

3.1

.;M

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.9

N;N

REVEL

Uncertain

0.60

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.016

D;D

Polyphen

1.0

.;D

Vest4

0.74

MutPred

0.47

.;Gain of MoRF binding (P = 0.0077);

MVP

0.61

MPC

1.1

ClinPred

0.96

GERP RS

5.4

Varity_R

0.41

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over